Augmentation of inorganic pyrophosphate elaboration in cartilage by serum factors

Abstract

The disordered production of inorganic pyrophosphate ( PP i) by articular cartilage is thought to have an important role in the pathogenesis of calcium pyrophosphate dihydrate deposition disease and perhaps osteoarthritis. We have previously shown that fetal calf serum added to the culture media of porcine articular cartilage explants increases the elaboration of PP i into the ambient media. We have examined this PP i stimulatory activity by studying the effects of adult human serum (HS), serum derived from adult human plasma (HP), and an acid-alcohol extract of human platelets (PE) on PP i production in cartilage organ culture. Ten percent HS produces a 1.4-fold increase in PP i production after 48 h of culture, while cartilage incubated in media containing 10% HP produces no more PP i than that incubated in media alone. PE stimulates a mean 2-fold increase in PP i production at 48 h in the presence of low concentrations of HP, and has no effect alone. It does not appear to up-regulate the activity of the ectoenzyme nucleoside triphosphate pyrophosphohydrolase (NTPPPH), nor does it promote the release of enzyme substrate into the extracellular space. Cartilage exposed to 0.5% HP and PE has 1.51 ± 0.36 units of NTPPPH activity whereas cartilage exposed to 0.5% HP alone has 1.52 ± 0.41 units of enzyme activity. PE does not increase the release of [ 14C]adenine-labeled compounds into the media. Approximately 13% of soluble 14C counts was found in the media of chondrocytes treated with PE while 18% of counts was released in the presence of HP alone. We have demonstrated a factor or factors present in FCS, HS, and an acid-ethanol extract of human platelets which represent(s) the first known physiologic modulators of PP i production in articular cartilage and may increase PP i production without affecting NTPPPH activity.